The transformation of cultured mammalian cells with defined DNA fragments has been explored as a system for studying eukaryotic gene regulation with a special interest in studying the expression of normal human globin genes and to characterize and ultimately correct the molecular defects affecting globin gene expression in patients with homozygous beta-thalassemia. The co-transformation of mouse fibroblasts with herpes simplex thymidine kinase gene and a recombinant bacteriophage, lambda H beta G1, containing both the human delta and beta globin genes has resulted in mouse cell lines in which the human globin genes are stably integrated without apparent rearrangement. Analysis of DNA from the transformed cells has identified the several Eco RI restriction endonuclease fragments which contain the globin genes. The human globin genes are expressed in the mouse cells for there are 75-100 copies of beta globin mRNA per cell as determined by molecular hybridization analysis. Nearly the entire coding sequence of the globin gene is represented in these transcripts, although the RNA molecules may be slightly shorter than authentic beta globin mRNA isolated from human reticulocytes. No human beta globin was detected by radioimmunoassay of extracts from the transformed mouse cells.